Preparation of11C-nitromethane and an example of its use as a radiolabeling precursor

Journal of Labelled Compounds and Radiopharmaceuticals-Vol. X W , No. 7

P R E P A R A T I O N O F l 1 C - N I T R O M E T H A N E A N D A N E X A M P L E

OF I T S USE AS A R A D I O L A B E L I N G PRECURSOR

Kar l -Olof S c h o e p s l ' 2 , C h r i s t e r H a l l d i n * " '3, S h a r o n

2 S t o n e - E l a n d e r ' , Beng t L5ngstrOm4 a n d T o r g n y G r e i t z

K a r o l i n s k a P h a r m a c y , B o x 6 0 0 2 4 , S - 1 0 4 01 S t o c k h o l m , Sweden

2 D e p a r t m e n t o f N e u r o r a d i o l o g y , K a r o l i n s k a H o s p i t a l , S - 1 0 4 01

S t o c k h o l m , Sweden

3 D e p a r t m e n t o f P s y c h i a t r y a n d P s y c h o l o g y , K a r o l i n s k a H o s p i t a l ,

S -10401 S t o c k h o l m , Sweden

4 D e p a r t m e n t o f O r g a n i c C h e m i s t r y , U n i v e r s i t y o f U p p s a l a , Box 531 ,

S -751 21 U p p s a l a Sweden

SUMMARY

N o - c a r r i e r - a d d e d l 1 C - n i t r o m e t h a n e h a s b e e n p r e p a r e d f r o m

' l C - m e t h y l i o d i d e i n a o n e - p o t r e a c t i o n b y u s e o f s i l v e r o r s o d i u m

n i t r i t e i n d i f f e r e n t s o l v e n t s . A c o n v e r s i o n o f u p t o 87% was o b t a i n e d

w i t h i n 3 m i n . I t c o u l d e a s i l y b e d i s t i l l e d from h i g h - b o i l i n g s o l v e n t s

t o a n o t h e r r e a c t i o n v e s s e l (14OoC, 3 m i n ) . I t s p o t e n t i a l a s a

r a d i o l a b e l i n g p r e c u r s o r i n c o n d e n s a t i o n s w i t h a l d e h y d e s was s h o w n i n

t h e s y n t h e s i s o f l l C - B - n i t r o s t y r e n e ( 8 5 % c o n v e r s i o n a f t e r 3 -5 m i n ) .

Key W o r d s : " C - n i t r o m e t h a n e , " C - n i t r o a l k a n e , 1 C - ! 3 - n i t r o s t y r e n e

i To whom c o r r e s p o n d e n c e s h o u l d b e a d d r e s s e d

0362 -4803/88/070749- 10W5.00 0 1988 by John Wiley & Sons, Ltd.

Received October 22, 1987 Revised November 16, 1987

750

INTRODUCTION

K.-0. Schoeps et al.

To u t i l i z e t h e d y n a m i c r e g i o n a l i n f o r m a t i o n o b t a i n e d b y p o s i t r o n

e m i s s i o n t o m o g r a p h y ( P E T ) f o r m o n i t o r i n g s p e c i f i c b i o c h e m i c a l

p r o c e s s e s , i t i s i m p o r t a n t t o s e l e c t a p p r o p r i a t e r a d i o l a b e l e d

c o m p o u n d s . I n o r d e r t o s y n t h e s i z e a n d l a b e l a d e s i r e d c o m p o u n d w i t h

a s h o r t - l i v e d p o s i t r o n - e m i t t i n g r a d i o n u c l i d e s u c h a s c a r b o n - 1 1 i n

a c e r t a i n p o s i t i o n , a w i d e r a n g e o f s u i t a b l e l a b e l e d p r e c u r s o r s is

n e c e s s a r y f o r s y n t h e t i c f l e x i b i l i t y . A n u m b e r o f s u c h p r e c u r s o r s m a y

b e a v a i l a b l e d i r e c t l y f rom t a r g e t i r r a d i a t i o n s o r b y r a p i d o n - l i n e

s y n t h e s i s . E x a m p l e s o f t h e s e " p r i m a r y " p r e c u r s o r s a r e C 0 2 ,

( ' ) r f S e c o n d a r y f f p r e c u r s o r s may a l s o b e

1 1

l 1 C 0 , H l 1 C N a n d 1 1 C H 4 .

o b t a i n e d from a l v p r i m a r y l f p r e c u r s o r i n b a t c h w i s e o r o n - l i n e

p r o d u c t i o n s . E x a m p l e s o f s u c h " s e c o n d a r y t 1 p r e c u r s o r s a r e

( 2 - 4 ) R - l ' C H O , (5-71 C O C l 2, ( 8 ) C H 3 Li (') a n d 1 1

C H ~ N ~ . ( l o )

R- C H 2 1 ,

T h e d e v e l o p m e n t o f t h e s e p r i m a r y a n d s e c o n d a r y

p r e c u r s o r s h a s p l a y e d a d e c i s i v e r o l e i n t h e s y n t h e s i s o f n e w

p o s i t r o n - e m i t t i n g r a d i o p h a r m a c e u t i c a l s .

T h e s y n t h e t i c v e r s a t i l i t y o f n i t r o a l k a n e s i n o r g a n i c s y n t h e s i s h a s

r e c e i v e d a c o n s i d e r a b l e a m o u n t o f a t t e n t i o n . W i t h a p K a = 1 0 . 2 , i t c a n

r e a d i l y b e c o n v e r t e d t o a n u c l e o p h i l e b y t h e a d d i t i o n o f b a s e . I n

a d d i t i o n t o u n d e r g o i n g c o n d e n s a t i o n a n d n u c l e o p h i l i c s u b s t i t u t i o n

-NOS Rbi=C.

/ VTNH'

R

Scheme 1

"C-Nitromethane and its use as o Radiolabeling Precursor 751

r e a c t i o n s , n i t r o a l k a n e s c a n b e c o n v e r t e d t o o t h e r f u n c t i o n a l i t i e s s u c h

a s c a r b o n y l c o m p o u n d s ( N e f ' s r e a c t i o n ) a n d t o a m i n e s ( S c h e m e 1 ) . One

e s p e c i a l l y i m p o r t a n t a p p l i c a t i o n o f t h e Nef r e a c t i o n is i n

c a r b o h y d r a t e c h e m i s t r y w h e r e n i t r o m e t h a n e can b e u s e d t o i n c r e a s e t h e

n u m b e r o f c a r b o n a t o m s i n a n a l d o s e b y o n e .

To i n v e s t i g a t e t h e p o s s i b i l i t y o f e x t e n d i n g t h e s e r e a c t i o n s t o

r a d i o l a b e l i n g w i t h p o s i t r o n - e m i t t i n g r a d i o n u c l i d e s , e m p h a s i s has b e e n

p l a c e d o n t h e s y n t h e s i s o f n i t r o m e t h a n e l a b e l e d w i t h c a r b o n - 1 1 , a s

p r e v i o u s l y b r i e f l y r e p o r t e d . ( l 1 C - N i t r o m e t h a n e was p r e p a r e d

v i a a n u c l e o p h i l i c s u b s t i t u t i o n r e a c t i o n e m p l o y i n g

i o d i d e i n a o n e - p o t r e a c t i o n by u s e o f s i l v e r o r s o d i u m n i t r i t e i n s i x

d i f f e r e n t s o l v e n t s (Scheme 2). A S i m p l e x o p t i m i z a t i o n m e t h o d ( 1 2 ) was

u s e d t o o p t i m i z e t h e r a d i o c h e m i c a l c o n v e r s i o n of " C - m e t h y l i o d i d e

i n d i m e t h y l f o r m a m i d e ( D M F ) a n d m e t h a n o l . T h e u t i l i t y o f

" C - n i t r o m e t h a n e a s a r a d i o l a b e l i n g p r e c u r s o r was d e m o n s t r a t e d b y

c o n d e n s a t i o n w i t h b e n z a l d e h y d e ( 1 3 ) t o y i e l d l l C - B - n i t r o s t y r e n e

( S c h e m e 3).

"C-methy l

sdvent - "CH,NO. "CHJ M+NO; heat

Scheme 2

scheme 3

R E S U L T S A N D DISCUSSION

I I C - N i t r o m e t h a n e c a n t h u s r a p i d l y b e p r e p a r e d by t h e r e a c t i o n o f

" C - m e t h y l i o d i d e w i t h s i l v e r - o r s o d i u m n i t r i t e . T h e y i e l d s

o b t a i n e d a f t e r 3 m i n r e a c t i o n t ime v a r i e d b e t w e e n 0-87% i n

n o - c a r r i e r - a d d e d e x p e r i m e n t s . I n i t i a l s t u d i e s f o c u s e d o n t h e i n f l u e n c e

752 K. -0. Schoeps et al.

o f e x p e r i m e n t a l f a c t o r s o n t h e p r o d u c t d i s t r i b u t i o n . As s u m m a r i z e d i n

T a b l e 1 , a n i n v e s t i g a t i o n was p e r f o r m e d o n t h e e f f e c t of v a r y i n g

s o l v e n t , metal n i t r i t e ( s i l v e r a n d s o d i u m ) a n d r e a c t i o n t e m p e r a t u r e

(room t e m p e r a t u r e a n d 100°C) w h i l e t h e a m o u n t o f s a l t a n d v o l u m e o f

s o l v e n t were h e l d c o n s t a n t . T h e c o n v e r s i o n o f ' l C - m e t h y l i o d i d e t o

l 1 C - n i t r o m e t h a n e p r o c e e d e d r e a d i l y i n t h e a p r o t i c p o l a r s o l v e n t s

a i m e t h y l s u l f o x i d e (DMSO) a n d DMF. Good y i e l d s were a l s o o b t a i n e d i n

t h e p r o t i c p o l a r s o l v e n t m e t h a n o l b u t h i g h e r t e m p e r a t u r e s were

r e q u i r e d . I n t h e l e s s p o l a r d i e t h y l e t h e r a p p r e c i a b l e a m o u n t s o f

" C - n i t r o m e t h a n e were o n l y o b s e r v e d w i t h s i l v e r n i t r i t e a t t h e

h i g h e r t e m p e r a t u r e . I n g e n e r a l h i g h e r y i e l d s were o b t a i n e d w i t h t h e

s i l v e r t h a n w i t h t h e s o d i u m n i t r i t e s a l t . L i k e w i s e , y i e l d s o f

" C - n i t r o m e t h a n e were g e n e r a l l y h i g h e r a t 100°C t h a n a t room

t e m p e r a t u r e .

Table 1. Surury of results regarding the product distribution in six different solvents, tro nitrite salts and two reaction temperatures.

Product Distribution ( Z )

Solvent H' T 11CH3W2 "CH30N0 11CH31

Dimethylsulfoxide Na AT 54 46 100 51 49

A9 RT 46 50 100 49 51

Dimethyl formanide Na RT 54 46 100 53 47

A 9 RT 54 46 100 07 13

Acetonitrile Na RT - - 100 100 19 17 65

A 9 AT 70 30 100 74 26

Isocapronitrile Na RT 100 100 - loo RT 16 7 75' 100 40 36 0.

kl

Na RT - loo 100 26 6 60 RT 20 7 73 100 74 6 10.

As

Diethyl Ether Na RT - 100 100 100

A9 RT 4 9). 100 51 4 0.

Solvent volrne = D 3 nin; *Rair&50?td%&vity ia an unidentified by-product

100 ng; Trapping temperature = RT; Reaction tine

llC-Nitromethane and its use as a Radiolabeling Precursor 753

' l C - M e t h y l n i t r i t e , a major b y - p r o d u c t o f t h i s r e a c t i o n , was i n

some c a s e s , f o u n d t o b e 51% o f t h e t o t a l a c t i v i t y . G e n e r a l l y , h o w e v e r ,

t h e r a t i o of l l C - n i t r o m e t h a n e t o " C - m e t h y l n i t r i t e i n c r e a s e d w i t h

i n c r e a s i n g t e m p e r a t u r e s . A n o t h e r l a b e l e d p r o d u c t was o b s e r v e d i n

i s o c a p r o n i t r i l e , m e t h a n o l a n d d i e t h y l e t h e r . T h o u g h u n i d e n t i f i e d , i t

m i g h t be a n i t r a t e e s t e r a r i s i n g from t h e r e a c t i o n o f t h e a l k y l h a l i d e

w i t h s i l v e r n i t r a t e w h i c h may b e f o r m e d d u r i n g t h e t h e r m a l

d e c o m p o s i t i o n o f s i l v e r n i t r i t e . ( 1 4 )

By u s e o f t h e o p t i m i z a t i o n m e t h o d ( S i m p l e x ) , t h e i n f l u e n c e of

t e m p e r a t u r e a n d a m o u n t o f s i l v e r n i t r i t e was i n v e s t i g a t e d i n DMF a n d

m e t h a n o l ( T a b l e s 2 a n d 3 , r e s p e c t i v e l y ) . I n b o t h ca ses y i e l d s seem t o

b e m o r e i n f l u e n c e d b y m a i n t a i n i n g a f a v o u r a b l e r e a c t i o n t e m p e r a t u r e

t h a n b y i n c r e a s i n g t h e a m o u n t of s i l v e r n i t r i t e . For e x a m p l e i n DMF,

l l C - n i t r o m e t h a n e was o b t a i n e d i n 80% r a d i o c h e m i c a l y i e l d w i t h 1 0 m g

Table 2. Suarnery o f results regarding the radiochemical yield in dimethylforclanide.

A W 2 (4 renp. COC, 11cH3N02 (%I "CH30N0 ( X I 11CH31 ( X I

10 0 23 5 72 10 80 81 19 0 10 100 80 20 0 10 123 80 20 0 20 175 68 32 0 50 64 82 18 0

loo 25 54 46 0 100 80 85 15 0 loo loo 87 13 0 100 123 76 24 0 100 175 68 32 0

Solvent volume = 0.5 11; Trapping terp. = R I ; Reaction time = 3 nin

Table 3. Slrary of results regarding the rdiochsnicsl yield in methanol.

ASNO2 (ng) Terp. (OC) 11CH,N02 ( X I %H30N0 (Z) 11CH31 ( X I

2 2 2 5

121 60 152 78 175 45 120 79

10 50 M 120 70 64 80 152 100 25 100 100 102 170

100 175 100 100

1 86 33 78 20 74 69 75 80

25 0' 22 0 30 17, 16 5 0 97 13 09 3 64 22 0 7 73 6 31 12 6

109 0 09 29

190 48 40 2 489 190 121 75 9 0'

Solvent volua = 0.5 nl; Trapping tsq. = RT; Reaction time I 3 nin; *Remainder o f radioactivity is an unidentified by-procbct

754

s i l v e r n i t r i t e a t 8 O o C ( T a b l e 2 ) . I n m e t h a n o l a r a d i o c h e m i c a l

c o n v e r s i o n o f 7 9 % c a n b e o b t a i n e d w i t h 5 mg s i l v e r n i t r i t e a t 12OoC

( T a b l e 3).

K. -0. Schoeps er a[.

T h e t r a p p i n g e f f i c i e n c y o f " C - m e t h y l i o d i d e i n t h e s i x s o l v e n t s

u s e d was i n v e s t i g a t e d by m e a s u r i n g t h e d i s t r i b u t i o n o f r a d i o a c t i v i t y

i n t h r e e v e s s e l s c o n n e c t e d i n s e r i e s t o t h e m e t h y l i o d i d e s y s t e m . The

f l o w r a t e was m a i n t a i n e d a t 2 9 mL/min ( 2 O o C ) , a n d 85-98% o f t h e

m e t h y l i o d i d e was t r a p p e d i n t h e f i r s t r e a c t i o n v e s s e l ( T a b l e 4 ) .

Table 4. Trapping efficiency o f "C-methyl iodide in the reaction mixtures studied.

Solvent Trapping eff. (%)**

Mlso 85

Isocapronitrile' 98

Dm. 96 Acetonitrile 96

Hethanol' 92 Oiethyl Ether' 92

Temperature = RT; Flow I 29 ml/min; Solvent volume = 0.5 ml; Amount of AgN02 I 50 mg; *undissolved; "Calculated from the trapped- and total amount of lk-nethyl iodide

The t o t a l s y n t h e s i s t ime from E O B ( " ? - c a r b o n d i o x i d e ) was 1 3 min

( i n c l u d i n g p r e p a r a t i o n o f " C - m e t h y l i o d i d e ) . " C - N i t r o m e t h a n e

c o u l d e a s i l y b e d i s t i l l e d t o a n o t h e r r e a c t i o n v e s s e l (14OoC, 3 m i n )

f r o m DMF o r i s o c a p r o n i t r i l e . l 1 C - B - N i t r o s t y r e n e was p r e p a r e d v i a a

c o n d e n s a t i o n r e a c t i o n b e t w e e n b e n z a l d e h y d e a n d " C - n i t r o m e t h a n e ( 8 5 %

c o n v e r s i o n a f t e r 3-5 m i n ) . F u r t h e r e x a m p l e s o f t h e s y n t h e t i c u t i l i t y

o f " C - n i t r o m e t h a n e a s a r a d i o l a b e l i n g p r e c u r s o r a r e p r e s e n t l y u n d e r

i n v e s t i g a t i o n a s w e l l a s t h e d e v e l o p m e n t o f a n o n - l i n e p r o d u c t i o n

m e t h o d .

EXPERIMENTAL

G E N E R A L

T h e ' l C - c a r b o n d i o x i d e was p r o d u c e d a t t h e K a r o l i n s k a H o s p i t a l w i t h

a S c a n d i t r o n i x R N P 1 6 c y c l o t r o n u s i n g 1 6 MeV p r o t o n s i n t h e 1 4 N ( p , a )

"C r e a c t i o n . T h e gas t a r g e t was i r r a d i a t e d i n a b a t c h p r o d u c t i o n .

T h e " C - c a r b o n d i o x i d e p r o d u c e d was t r a p p e d i n a s t a i n l e s s s t e e l

"C-Nitromethane and its use (LF a Radiolabeling Precursor 755

c o i l c o o l e d w i t h l i q u i d n i t r o g e n b e f o r e b e i n g t r a n s f e r r e d t o t h e

o n e - p o t " C - m e t h y l i o d i d e s y s t e m . ( 5 , A n a l y t i c a l r e v e r s e d - p h a s e

H P L C was p e r f o r m e d u s i n g a n LDC C o n s t a m e t r i c I pump, a R h e o d y n e

i n j e c t o r ( 7 1 2 5 w i t h a 1 0 0 pL l o o p ) , a Waters p - B o n d a p a k C-18 c o l u m n

( 3 0 0 x 7 . 8 m m ) a n d a n E R M A U V d e t e c t o r ( 2 5 4 nm) c o u p l e d i n s e r i e s w i t h

a B e r t h o l d L B 503 d e t e c t o r . A c e t o n i t r i l e a n d 0.01 M p h o s p h o r i c a c i d

( 5 0 / 5 0 ) was u s e d a s t h e m o b i l e p h a s e w i t h a f l o w r a t e o f 3 .5 mL/min .

I n t e g r a t i o n o f t h e U V a b s o r b a n c e a n d r a d i o a c t i v i t y was a c c o m p l i s h e d

u s i n g a S h i m a d z u C-R2AX two c h a n n e l d a t a p r o c e s s o r . S i l v e r a n d

p o t a s s i u m n i t r i t e were o b t a i n e d f r o m F l u k a , b e n z a l d e h y d e , n i t r o m e t h a n e

a n d m e t h y l i o d i d e from Merck a n d 0 - n i t r o s t y r e n e f r o m A l d r i c h . M e t h y l

n i t r i t e was s y n t h e s i z e d b y a l i t e r a t u r e m e t h o d . ( 1 6 ) A l l o t h e r

s o l v e n t s a n d r e a g e n t s u s e d were a v a i l a b l e c o m m e r c i a l l y a n d o f

a n a l y t i c a l g r a d e .

C - N I T R O M E T H A N E ( S c h e m e 2 ) I I

' l C - M e t h y l i o d i d e was t r a p p e d i n a r e a c t i o n v e s s e l ( 1 . O mL

m i n i - v i a l , A l l t e c h ) a t room t e m p e r a t u r e , c o n t a i n i n g a m a g n e t i c

s t i r r e r , 0 . 5 mL s o l v e n t a n d a metal n i t r i t e s a l t . A f t e r s t i r r i n g f o r

3 m i n a t t h e d e s i r e d t e m p e r a t u r e , a n a l i q u o t was r e m o v e d , a d d e d t o

1 m L o f t h e m o b i l e p h a s e p r e c o o l e d i n d r y i c e / e t h a n o l / w a t e r m i x t u r e

( -10 ' t o - 3 O o C ) , a n d s t o r e d a s s u c h u n t i l t h e LC a n a l y s i s was

p e r f o r m e d . T h e r a d i o a c t i v e c o m p o n e n t s e l u t e d w i t h same r e t e n t i o n times

a s s t a n d a r d r e f e r e n c e s a m p l e s o f m e t h y l n i t r i t e , n i t r o m e t h a n e , a n d

m e t h y l i o d i d e ( 3 . 2 , 4 . 0 , a n d 5 . 6 m i n , r e s p e c t i v e l y ) . T h e u n i d e n t i f i e d

p r o d u c t e l u t e d a t 4 . 6 m i n . A t y p i c a l LC c h r o m a t o g r a m

(UV-absorbance/radioactivity) i s s h o w n i n F i g u r e 1 .

756 K.-0. Schoeps et al.

Figure 1. Analytical HPLC chromatogram (Radioactivity UV- Absorbance) A: 11CH30N0, 8: 11CH3NOZ, C= unident. D= 11CH31

CPM and

C- 6 - N I T R O S T Y R E N E ( Scheme 3)

' l C - M e t h y l i o d i d e was t r a p p e d i n a t w o - n e c k e d r e a c t i o n v e s s e l ( 1 0

m L , c o n n e c t e d w i t h a V i g r e u x c o l u m n ) c o n t a i n i n g a magnet ic s t i r r e r a n d

a s u s p e n s i o n o f 30 mg s i l v e r n i t r i t e in 0 . 5 mL i s o c a p r o n i t r i l e a t room

t e m p e r a t u r e . T h e m i x t u r e was h e a t e d a t 100 ' C f o r 3 m i n f o r

c o n v e r s i o n o f t h e m e t h y l i o d i d e . U n d e r a s t ream of n i t r o g e n t h e

" C - n i t r o m e t h a n e was s u b s e q u e n t l y d i s t i l l e d w i t h i n 3 m i n a t 14OoC

t o a 5 mL c o n i c a l v e s s e l ( a t -10' t o -2OOC w i t h d r y

i c e / e t h a n o l / w a t e r c o n t a i n i n g 0 . 5 m L m e t h a n o l a n d a magne t i c s t i r r e r .

B e n z a l d e h y d e ( 1 0 6 mg, 1 . 0 mmol) a n d s o d i u m h y d r o x i d e ( 2 5 pL, 1 0 M I

were a d d e d . A y e 1 ow c o l o r a p p e a r e d a f t e r a d d i t i o n of i c e - w a t e r ( 2 0 0

p L ) a n d h y d r o c h l o r i c a c i d ( 1 m L , 6 . 0 M I . An a l i q u o t was r e m o v e d a n d

s t o r e d f o r LC a n a l y s i s a s d e s c r i b e d a b o v e . A t a f l o w o f 3 . 5 m L / m i n

" C - B - n i t r o s t y r e n e e l u t e d a f t e r 8 . 9 m i n w i t h t h e same r e t e n t i o n t i m e

a s t h e r e f e r e n c e s a m p l e .

llC-Nitromethane and its use as a Radiolobeling Precursor

ACKNOWLEDGEMENTS

757

T h e a u t h o r s w o u l d l i k e t o t h a n k M r G o r a n P r i n t z f o r a s s i s t a n c e w i t h

t h e r a d i o n u c l i d e p r o d u c t i o n a n d Ms Camil la F a l k a n d Ms Lena L i n d b e r g

f o r t e c h n i c a l a s s i s t a n c e . T h i s w o r k h a s b e e n s u p p o r t e d b y g r a n t s from

t h e S w e d i s h M e d i c a l R e s e a r c h C o u n c i l , t h e Bank o f S w e d e n ' s

T e r c e n t e n a r y f u n d , t h e K a r o l i n s k a I n s t i t u t e , t h e N a t i o n a l I n s t i t u t e o f

M e n t a l H e a l t h a n d t h e S w e d i s h N a t u r a l S c i e n c e R e s e a r c h C o u n c i l w h i c h

i s g r a t e f u l l y a c k n o w l e d g e d .

REFERENCES

1 . C h r i s t m a n D.R., F i n n R.D., Karlstrom K . I . a n d Wolf A . P . I n t . J .

A p p l . R a d i a t . I s o t . 26: 4 3 5 ( 1 9 7 5 )

2 . Comar D., M a z i e r e M . a n d C r o u z e l C . - R a d i o p h a r m a c e u t i c a l s a n d

L a b e l l e d Compounds Vol. 1 . I A E A , V i e n n a , ( 1 9 7 4 )

3 . L & n g s t r o m B . , A n t o n i G . , G u l l b e r g P . , H a l l d i n C . , NBgren K . ,

R i m l a n d A . a n d S v l r d H . - A p p l . R a d i a t . I s o t . 21: 1 1 4 1 ( 1 9 8 6 1

4 . C r o u z e l C . , L a n g s t r o m B . , P i k e V . W . a n d C o e n e n H . H . - A p p l .

R a d i a t . I s o t . 38: 6 0 1 ( 1 9 8 7 )

5 . Berger C. , Maziere M . , S a s t r e J . a n d Comar D . - J . L a b . Comp.

R a d i o p h a r m . g: 5 9 ( 1 9 8 0 )

6 . T a n g D . Y . , L ipman A . , M e y e r C . J . , Wan C . N . a n d Wolf A.P. - J . Lab .

Comp. R a d i o p h a r m . 16: 4 3 5 ( 1 9 7 9 )

7 . H a l l d i n C . a n d L s n g s t r o m B. - Acta Chem. S c a n d . 38: 1 ( 1 9 8 4 )

758 K. -0. Schoeps et al.

8 . R o e d a D . a n d Westera C . - I n t . J . A p p l . R a d i a t . I s o t . 32: 9 3 1

( 1 9 8 1 1

9 . R e i f f e r s S., V a a l b u r g W . , Wiegman T . , Wynberg H . a n d W o l d r i n g

M.C. - I n t . J . A p p l . R a d i a t . I s o t . 14: 535 ( 1 9 8 0 )

1 0 . C r o u z e l C . , Amano R . a n d F o u r n i e r D . - A p p l . R a d i a t . I s o t . 38: 6 6 9

( 1 9 8 7 )

1 1 . H a l l d i n C . , S c h o e p s K - O . , S t o n e - E l a n d e r S . , L a n g s t r o m B . a n d

T h o r e l l J-0. - J . N u c l . Med. 28: 6 3 6 ( 1 9 8 7 )

1 2 . R i m l a n d A . , B e r g s o n G . , O b e n i u s U . , S j o b e r g S. a n d L h g s t r o m B .

A p p l . R a d i a t . I s o t . 38: 6 5 1 ( 1 9 8 7 )

1 3 . W o r r a l l D . E . - Org. S y n . , C o l l . Vol. 1, 4 1 3 ( 1 9 4 1 )

1 4 . K o r n b l u m N . - Org. R e a c t i o n s , 2: 1 0 1 ( 1 9 6 2 )

15. J o h n s t r o m P . , E h r i n E . , S t o n e - E l a n d e r S. a n d N i l s s o n J . L . G . - Acta

Pharrn. S u e c . 1: 1 8 9 ( 1 9 8 4 )

1 6 . S l a t e r W . K . - J . Chern. SOC. 117: 587 ( 1 9 2 0 )